Antiseptic



UNITED STATES PATENT OFFICE ANTISEPTIO Robert R. Burtner, Niles Center, 111., assignor to G. D. Searle & 00., Chicago, Ill., a corporation of Illinois No Drawing. Application February 3, 1938, Serial No. 188,572

2 Claims. (Cl. 167-71) This invention relates to antiseptics, and more decarboxylation of furoic acid, in 2100 cc. of particularly to germicidal compounds of the ethanol, chilled to 10 and added to a solution of organic mercury type. 1350 g. (5.0 moles) of mercuric chloride and 2710 The primary object of the invention is toprog. (20.0 moles) of sodium acetate in 30 l. of water 5 vide a substance which not only possesses high which has been previously cooled to The I antiseptic powers against micro-organisms, but is bottle should be immediately tightly stoppered also relatively non-irritating to body tissue. and allowed to stand for two days at laboratory Another object is to provide an organic mertemperature with occasional shaking. The crude cury compound antiseptic of relatively higher mercurial may then be filtered out, air dried and i0 solubility, but of lower toxicity to the tissues of crystallized from 10 l. of ethanol. The yield of 10 the host, than other organic mercury derivatives pure white 2-chloromercurifuran melting at 153 heretofore used for like purposes, Will be about 550 g. Additional amounts Of 1988 It has been discovered that these and other pure material may be recovered from the alcoholic related objects may be advantageously attained mother liquor by dilution with water. Also about by the use as antiseptics of certain mercurials of 410 g. of 2,5-dichloromercurifuran may be obthe furan series. As a result of extended investitained as an insoluble precipitate during crystalgations, it would appear that all derivatives of lization. any of the isomeric furylmercurials are suitable A solution of furylmercuric hydroxide may be for use as antiseptics, and that all of these comprepared by adjusting the pH of a suspension of pounds, while varying somewhat in effectiveness furylmercuric chloride in water to 9.2 by cautious 20 between one another, are relatively non-irritating addition of dilute alkali. to body tissue and of relatively high toxicity to Furylmercuric acetate may be prepared by micro-organisms when compared with most other treating a methanol solution of furylmercuric known antiseptics. Among the compounds by the chloride with silver acetate, filtering out the pre use of which successful antiseptic results have cipitated silver chloride, evaporating the filtrate 26 been obtained are 2-furylmercuric chloride and its to dryness, and crystallizing the residue from 5-methyl-, fi-tertiary butyl-, 5-bromoand 5- water-acetone solution. By using silver nitrate Intro-derivatives; B-furylmercuric chloride and in the same manner the basic furylmercuric its 2,5-dimethyl derivative; and 5,5-dinitronitrate may be obtained.

30 2,2'-difuryl-mercury. Furylmercuric chloride, bromide or iodide may 80 The derivatives of the isomeric iurylmercurials be prepared by the addition of one equivalent of falling within the scope of the present invention the desired sodium halide to a saturated aqueous may be represented by the formulae. solution of furylmercuric acetate.

' 2-ch1oromercurifuran, 5-bromo- 2- chloromercurifuran, 5-methyl-2-chloromercurifuran, 5-iso- 5 and I propyl-2-chloromercurifuran, 5-tertiary butyl-2- R chloromercurifuran, 5 -tertiary amyl-2-chloromercurifuran and 5-hexyl-2-chloromercurifuran wherein R and may be CH3, (331-17, C4319, may be prepared from furoic acids by preparing a 40 CSHH, 1 Br, or N02, and X may be the anion of solution of one mole of the sodium 5-substituted- 0 any acid, whether organic or inorganic, such as z-fllroate (made by dissolving the acid in exactly 1 Br, 1, N03, 01-1 000 H2303, B02 and one equivalent of sodium hydroxide) in 0.5-5.0 l. O C6H2(NO2)3, 0 or of water at laboratory temperature. This is added to a solution of one mole of mercuric chlov p ride, and after one hour the mixture is-filtered 5 N and then refluxed until the evolution of carbon dioxide is complete. On cooling, the mercurial 0 may be filtered and crystallized from ethanol. The expressions used are intended to be general These 'mercm'ials (except 5'bromo'2'chlommer' so as to include the various positionalisomers. curifuran) may also be Prepared by mercuration 60 The furan mercurial antiseptics of the present of e alkyl furans in the Same manner as invention may be prepared in any suitable mandescribed above for the mercuration of furan. ner. For example, 2-chloromercurifuran (furyl- 5-nitro-2-'chloromercurifur y be P p mercuric chloride) may be obtained from a soluby heating an aqueous solution of sodium 5-nitrotion of 340 g. (5.0 moles) of furan, prepared by Z-furoate (0.4 mole) and 0.8 mole of mercuric I there may be recovered 50% of the original 5-nitro-2-furoic acid.

To prepare 3-chloromercurifuran, acetoxymercury furoate or its equivalent is first prepared by adding a solution of 366 g. (3 mols) of furoic acid in 3 l. of water to a stirred solution of 477 g. (1.5 moles) of mercuric acetate in 75 l. of water. The precipitate should be filtered out and air dried, giving a yield of about 490 g. 740 g. of the acetoxymercury furoate should then be spread out in a thin layer over the bottom of a suitable container placed on a hot plate at 140 for two days. 900 cc. of 95% acetic acid, wherein it will dissolve in about twenty-four hours with slight heat evolution. This solution should then be poured into 8 l. of water, filtered and the filtrate treated with sodium chloride until no further precipitate is formed. The precipitate when filtered, washed I with water, and dried over a steam plate will yield about 270 g. of solid which should be extracted with ether in a Soxhlet apparatus for eight to ten hours. When the ether is evaporated it will leave about 95 g. of crude 3-chloromercurifuran which may then be crystallized from ethanol to yield about 87.5 g. of pure product melting at To prepare 2,2'-difurylmercury, add at once to a solution of 50 g. of sodium thiosulfate in 200 cc. of water 0.1 mole of 2-chloromercurifuran; the mixture should then be shaken vigorously for a few minutes, and after eight hours the precipitate filtered to give a 95% yield of crude difurylmercury which may be purified by crystallization from acetone-water solution. The pure product will melt at 114.

2,5-dimethylfuran may be mercurated in the same manner as furan to give a 50% yield of 2,5- dimethyl-3-chloromercurifuran melting at 164". The furyl mercuric compounds of the present invention are more soluble than other organic mercurials and may be prepared in more concentrated solutions for dispensing or other purposes. When used as antiseptics they are usually prepared in the form of glycerin, alcohol or other non-aqueous concentratesto which water is then The aqueous The material should then be suspended in In studying the properties of these furyl mercuric derivatives, the general principles as stated 'by Salle and co-workers were employed. This consists in determining the concentrations of antiseptic which kill Staphylococcus aureus and Bacterium coli on ten minute exposure, and comparing this with the maximum concentration whichis not fatal to embryonic heart tissue on 24 hour exposure. The embryonic heart tissue is chosen as being analogous to living tissue in general, and is used to determine the degree of irritation produced by the antiseptic in question. Typical data on the antiseptic action are as follows:

Killing dilutions in 24 hours In the tissue culture experiments the compounds were found tobe relatively non-irritating, as compared to their antiseptic value against bacteria.

Extended clinical investigations have also been made as to the antiseptic properties of the furan mercurials of the present invention wherein it has been established that these substances are both highly antiseptic in their action on microorganisms and relatively non-irritating to body tissue. Simply by way of example, it may be noted that a solution of 2-furylmercuric chloride, one of the preferred forms of the invention, has been used in the human eye with marked antiseptic efl'ect but without injury to the eye.

There is thus provided by the present invention a new antiseptic of the organic mercury type which is of improved characteristics of various respects, and of highly effective and dependable action for the purposes intended.

This application is limited to the particular species defined in the appended claims, the generic aspects of the invention and certain of the other species being the subject matter of copending'application Serial No. 276,719, filed May 31, 1939.

What is claimed is:

' 1. An antiseptic preparation for use in contact with human tissue comprising furylmercuric chloride.

2. An antiseptic preparation comprising 2-furylmercuric chloride. ROBERT R. BUR'I'NER. 

